1. Field of the Invention
This invention relates to an irradiation device for therapeutic purposes, especially for the acute or chronic treatment of totally or partially cell-mediated inflammations of the skin, connective tissue and internal organs, viral and other infectious diseases such as HIV or prion infections, fungal diseases of the skin and the mucous membranes, bacterial diseases of the skin and the mucous membranes as well as hand eczema or anal eczema.
2. Brief Description of the Related Art
Therapeutic irradiation arrangements have been known for a long time, especially in the field of phototherapy of skin diseases. According to the particular application the patient is irradiated with wavelengths between 315-1500 nm. Particularly the range of wavelengths between 315-340 nm (UV-A2) carries an increased risk of carcinogenesis; so that especially in the treatment of atopic eczema the UV-A1 therapy (340-400 nm) is used.
Photochemotherapy as a general term includes the general use of optic irradiation for the attainment of therapeutic effects. A subspecialty of photochemotherapy is the photodynamic therapy (PDT). The main fields of PDT application are cancer treatment and the treatment of totally and partially cell-mediated skin inflammations. A common trait of both PDT applications is the generation of reactive oxygen species. This is accomplished by the optical radiation which excites systemically or topically applied dye molecules which are converted into an excited state. Through interaction with existing oxygen molecules reactive oxygen species are generated which then damage or destroy the cell.
Cancer therapy with PDT, which aims at the destruction of tumor cells, divides into two fields of application: The main indication is the treatment of the viscera. The procedure includes the optical irradiation of a laser being transported to the tumor via an optic fiber, thus irradiating a small punctiform area. In addition, the patient receives photosensitizers.
This presents the problem of a decreased perfusion of tumor tissue and therefore a decrease in oxygen in that part, which also limits the generation of reactive oxygen species. Therefore it is known practice in the tumor treatment of the viscera with PDT to have the patient inhale oxygen in order to increase the oxygen content of the tumor tissue and so encourage the generation of reactive oxygen species. Because of the increased consumption of oxygen it is known to pulse the irradiation source so that in the pulse-off interval fresh oxygen is allowed to diffuse into the tissue.
The second field of tumor treatment with PDT is the treatment of superficial tumors such as especially melanoma, where no additional oxygen is given because of the naturally existing oxygen.
Other than tumors, wholly or partly cell-mediated skin inflammations usually cover large areas of skin, so that irradiation sources which can cover larger areas, for example 5 cm2-2 m2 at a time, are the medium of choice here. Another difference to tumors is the increased blood flow in inflammations that is recognizable by an erythema in the inflamed area. Furthermore, there is no exogenous application of sensitizers, so that even if we assume a phototherapeutically induced involvement of singlet oxygen (for example, by using the photodynamic effect of endogenous porphyrins) we can conclude that even a considerable decrease of oxygen concentration has little or no important effect on the decrease of triplet efficiency in the skin. Besides this, the maximum concentration of endogenous photosensitizers is several orders of magnitude below the concentration which can be effected by systemic or topical application. The aforementioned good perfusion is the reason that a combined photo/oxygen therapy has not been tried yet in the treatment of cell-mediated diseases.
The PDT method that is chiefly used in the treatment of wholly or partly cell-mediated diseases is a high-dose UVA1-Therapy, using a wavelength range between 340-400 nm. This requires the employment of high doses of, for example, over 60 mW/cm2 to get satisfactory therapeutic effects. In spite of that, 20-30% of the treated patients do not respond to a UVA1-Therapy.
It is known to treat acne, which is a skin disease caused by proliferation of bacteria in blocked follicles of areas of the skin that are rich in sebaceous glands together with keratosis, with blue light in the range of 400-440 nm without significant proportions of UVA, with limited success.
Here we refer to the article of V. Sigurdsson et al., Phototherapy of Acne Vulgaris with visible Light, Dermatologie 1997, 194; Iss.3, 256-260 which includes further literature references. This form of therapy started by using red fluorescence of acne follicle as part of the dermatological examination using Wood's Lamp. The source determined for the fluorescence was the storage of large quantities of porphyrins in the propionbacterium acne. McGinley et al., Facial follicular porphyrin fluorescence. Correlation with age and density of propionibacterium acnes, Br. J. Dermatol. 1980, Vol. 102, Iss. 3, 437-441). Since the principal absorption (Soret-band) of porphyrins is around 420 nm, it was obvious for Meffert et al. to treat acne follicles with blue light. The longest-wave absorption band of porphyrins is 630 nm, with a penetration depth of 4 mm, which is most favorable for photodynamic follicle treatment and is used for this purpose.
From WO 00/02491 such an irradiation device is known which comprises at least one narrowband spectrum in the range of 405-440 nm. As alternative or cumulative areas of the spectrum the wavelength intervals between 610-670 and 520-550 nm are given. For further improvement of treatment efficacy it is proposed to increase the oxygen concentration within the irradiated area by applying oxygen-enriched emulsions before or during the irradiation. The irradiation intensity for this is between 10-500 mW/cm2.
From EP 0 565 331 B1 a device for the treatment of vascular diseases in an area of the skin is known, including a housing with an incoherent light source mounted in that housing and suitable for the emission of pulsed light for treatment, and an opening in the housing, defining a ray of light which is emitted onto the afflicted area of skin without passing through a cable of optical fibers, thus showing a wider irradiation area than devices with optical fibers, the device also including a low cutoff filter, thus cutting off the visible and UV parts of the spectrum while the incoherent light source emits a ray of light combining wavelengths between 300 and 1000 nm. The light source has an electrical connection to a pulse-forming-network in order to deliver a time pulse between 1 and 10 ms, the emitted ray of light producing an energy density between 30 and 100 J/cm2, so that the emitted light may pass through a low cutoff filter and penetrate the skin as deeply as desired without burning of the skin, in order to heat a blood vessel under the skin in the skin treatment area and to cause blood coagulation in the blood vessel. The blood coagulation described there is to be avoided in the treatment of wholly or partially cell-mediated skin inflammations or acne, so that the described device is not suitable for PDT.
From U.S. Pat. No. 5,964,749 an irradiation device for the tightening of skin is known, including a source of irradiation emitting pulsed light in the range of 600-1200 nm, by which heat is coupled into the tissue below the threshold of necrosis, causing the collagen of the skin to shrink. The pulse energies here range mostly around 1 J/cm2. The pulse irradiation peaks show a power of 100-1000 W/cm2. The preferred total energy for one treatment is given as 100 J/cm2.
From WO 00/53114 an irradiation arrangement for skin tightening is known, including an irradiation source emitting pulsed light in a wavelength interval of 500-850 nm, the pulse energy being less than 5 J/cm2.
From WO 00/28575 a irradiation arrangement for therapeutic and cosmetic purposes is known for the treatment of primarily T-cell-mediated skin diseases, especially of atopic dermatitis, cutaneous T-cell-lymphoma, lichen ruber, alopecia areata, systemic Lupus erythematodes and psoriasis, the irradiation device comprising at least one source of optical irradiation, generating on the afflicted area an intensity of at least 2 mW/cm2 in a wavelength interval of 400-440 nm, and less than 21% of that intensity in a wavelength interval of 300-400 nm. The irradiation device utilizes the astonishing efficiency of the radiation in the range of 400-440 nm, which offers an irradiation device for the treatment of primarily T-cell mediated skin diseases with which it would be possible to treat skin diseases like lichen ruber that have so far almost defied treatment, and, due to its drastically reduced carcinogenity over UVA, also offers the possibility for the treatment of children.
This patent also mentions the fact that for the mode of efficiency of blue light there are patient-specific threshold values for the intensity of irradiation. This statement is based on the specific content of melanin and/or antioxidants in each patient's skin, so that irradiation intensities of over 60 mW/cm2 resp. over 100 mW/cm2 are preferably applied.
From EP 0 726 083 A2 a therapeutic irradiation arrangement for the treatment of cancer cells in tissue is known, which features a diagnostic and a treatment mode. The source of radiation is a broadband flashlamp the spectrum of which is modified by filters according to the operation mode. In treatment mode the source emits light in the range of 600-1000 nm or 600-700 nm, the pulses showing an energy density between 0.1-20 J/cm2. The intensity here is between 100-2000 mW/cm2. The diagnostic mode utilizes the fluorescence of cancer cells in blue light. This fluorescence can be recorded and analyzed with a suitable optical arrangement. For this purpose, the tissue to be examined is irradiated with pulses of a spectral range between 350-500 nm with a peak at 400 nm. The pulse frequency lies between 0.02-2 Hz, with a pulse length between 0.1-1000 ms. The light is coupled into a quartz cylinder or an optic fiber with an energy density between 0.02-4 J/cm2. The size of the examined area depends on the distance between quartz cylinder resp. optic fiber and skin surface. Due to the non-coherence of the radiation, only a fraction of the radiation energy can be coupled into the optic fiber. It is, however, possible to couple most of the energy into the quartz cylinder, but here the light rays are extremely expanded on leaving the cylinder. On an area of, for example, 0.5 cm2 and an observation distance of 5 cm the energy density on the treatment decreases by a factor of 500. These observation distances are, however, necessary in order to watch the fluorescence, which is illustratively described in U.S. Pat. No. 6,021,344. This causes a rather low energy density of 0.04-8 mJ/cm2 on the skin, which is sufficient for diagnostic purposes.